The overall objective of this project is to assess the risk of emergence of new HIV types from SIV-infected persons in Cameroon. This objective will be obtained by using a new strategy for testing for persons naturally infected with SIV, characterizing their infections and testing for infection in their contacts. Both sexual and causal contacts will be studied. The feasibility of such a project was recently established in preliminary studies using SIV assays in Anglophone Cameroon. We tested 1536 persons attending clinics in and near Kumba, Cameroon for any reason, mostly fevers and other acute illnesses. We used western blots followed by SIV-specific SIV peptide ELISA on all positive and indeterminants results. This new approach identified 6 persons with SIV antibody, 1 SIVcpz, 1 SIVagm and 2 each for SIVrcm and SIVmnd. Aim 1. To screen the general human population in Southwest Cameroon for SIV infections. We will use antibody assays that have already been validated in this region. We will also employ PCR-based testing. Aim 2. To characterize the virologic and phylogenetic properties of SIV either isolated or amplified from humans in Cameroon. For example, we will test G->A hypermutation for testing for adaptation of SIV to humans. Aim 3. To characterize the epidemiology and natural history of SIV infections in humans exposed to simian viruses. We will examine replication, transmission and pathogenesis. Contacts will be tested to determine if these retroviruses are transmissible between humans. The outcome of these infections in humans will be addressed. SIV antibody + persons will have repeated clinical follow-ups. Thus far, SIV-like infections in humans have been dead end infections. This approach will enable us to find and track SIV human infections to assess the risk for emergence of new HIVs. Other groups both French and American are working in Cameroon, but the relatively low sero-prevalence for these viruses warrants other groups being funded to increase the chances of finding active SIV infections in the acute stage. PUBLIC HEALTH RELEVANCE: The root causes for the emergence of the AIDS viruses remain unknown even though this knowledge is vital to prevent the emergence of new epidemics. Although simian immunodeficiency viruses (SIVs) in Africa have been identified as the original source of the AIDS viruses, nothing is known as to why 2 different SIVs suddenly emerged to become epidemic human AIDS viruses in the 20th century. This project will trace the natural history SIV infections in humans to understand how the AIDS epidemic began.